1591P - Primordial germ cell as potent cell of origin of mucinous cystic neoplasms of the pancreas and mucinous ovarian tumors

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Pathology/Molecular Biology
Basic Scientific Principles
Presenter Intidhar Labidi-Galy
Citation Annals of Oncology (2016) 27 (6): 545-551. 10.1093/annonc/mdw393
Authors I. Labidi-Galy1, K.M. Elias2, P. Tsantoulis1, A. Vitonis2, L. Doyle3, J. Hornick3, D.W. Cramer2, M. Goggins4, C.L. Kerr5, M. Birrer6, M. Hirsch3, R. Drapkin7
  • 1Department Of Oncology, Hôpitaux Universitaires de Genève - HUG, 1205 - Geneva/CH
  • 2Department Of Obstetrics And Gynecology, Brigham and Women's Hospital, MA 02115 - Boston/US
  • 3Department Of Pathology, Brigham and Women's Hospital, MA 02115 - Boston/US
  • 4Department Of Pathology, Johns Hopkins University, MD21287 - Baltimore/US
  • 5Department Of Biology, University of Maryland School of Medicine, MD 21201 - Baltimore/US
  • 6Hematology/oncology, Massachusetts General Hospital, 02114 - Boston/US
  • 7Department Of Obstetrics And Gynecology, Penn Ovarian Cancer Research Center, PA19104 - Philadelphia/US

Abstract

Background

Mucinous ovarian tumors (MOT) are among the rarest and least studied epithelial ovarian neoplasms. Teratoma-associated MOT have been shown to be of germ cell origin. However, the pathogenesis of MOT not associated with teratoma remains unclear. Recent exome sequencing studies revealed similarities between MOT and mucinous cystic neoplasms (MCN) of the pancreas with frequent mutations in KRAS and RNF43.

Methods

Here we investigated the clinical characteristics of a series of 23 MCN and 287 MOT, which included age at diagnosis, sex, stage and exposure to smoking. We compared the immunohistochemical patterns of 23 MCN and 18 MOT (CK7, CK20, CDX2, MUC2, PAX8, SMAD4 and ß-catenin). We analyzed the gene expression profile (GEP) of 19 normal pancreatic tissues, 36 pancreatic ductal adenocarcinomas (PDAC), 6 MCN, 8 MOT, 27 normal fallopian tubes (FT), 13 high-grade serous ovarian carcinomas (HGSOC), 6 ovarian surface epithelium (OSE), 2 human PGCs and single cell RNA-sequencing of 5 primordial germ cells (PGC).

Results

We observed that both MOT and MCN occur mainly in young women that have been exposed to smoking and they are frequently diagnosed at early stages. Both tumors have similar immunohistochemical phenotype, mainly CK7 + CK20-MUC2-CDX2-. Thus, we hypothesize that MCN and MOT would share a common cell of origin, primordial germ cells (PGCs) that stopped in the dorsal pancreas during their descent to gonads during early human embryogenesis. We compared GEP of MOT, HGSOC, OSE, FT and PGCs. Alterations in MOT correlated more with PGCs whereas HGSOC correlated with OSE or FT. We also compared GEP of normal pancreatic tissue, PDAC, pancreatic MCN and PGCs. Molecular alterations in pancreatic MCN correlated more with PGCs whereas PDAC relied on normal pancreatic tissue.

Conclusions

These finding support a common molecular pathway for the development of MCN and MOT and suggest that both tumors can derive from PGCs. Pancreatic MCN would arise from embryological remnants of PGCs that stop in the pancreas during early developement. In the ovaries, MOT can develop from PGCs that would not undergo oogonia.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

Fondation de France, Arthur Sachs/Harvard

Disclosure

All authors have declared no conflicts of interest.